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‘Silenced’ gene is passed on
By Kate Dalke

Scientists have "turned off" a specific gene in mice, and demonstrated that the same gene is silenced in their progeny. They used a technique, called RNA interference, to interrupt the gene's ability to make a specific protein.

"The study marks the first time RNA interference against a specific gene has been passed on from generation to generation in an animal," says Michelle Carmell of Cold Spring Harbor Laboratory in New York, who led the study.

Gel shows targeted gene, Neil1, is "turned off" in mice with RNA interference (shRNA).

The technique could be used to make mouse models for studying human disease. Traditionally, scientists have studied specific genes in mice by "knocking-out" the gene, and then observing what happens, but the process is tedious.

Instead, the researchers used short pieces of RNA—called short hairpin RNAs—to target a gene involved in repairing damages in the genome. Cells with the silenced gene were more sensitive to radiation, and the scientists could see that the new technique was working.

Physically, the mice did not look any different, but Carmell says that is because other repair genes probably compensated for the silenced gene. She said it is still too early to tell if the mice will develop tumors.

The technique is "extremely specific" for silencing genes. If there's a miss-match in the sequence, the target won't be affected.

Why did they target a gene involved in DNA repair? "It's just the one that worked," says Carmell. She says they tried unsuccessfully to target genes that make crinkly ears or albino mice.

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Carmell, M.A. et al. Germline transmission of RNAi in mice. Nat Struct Biol. Published online January 19, 2003.

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